摘要：
Objective To investigate the expression of programmed death 1(PD-1) and programmed death ligand 1 (PD-L1) on T lymphocyte and monocyte from peripheral blood of advanced non-small-cell lung cancer (NSCLC) patients and its potential role in immune escape of NSCLC.Methods Forty-eight patients with advanced NSCLC (Lung Cancer Group) were included from the Department of Respiratory Diseases in The Second Affiliated Hospital of Soochow University from June 2014 to June 2015.Thirty-six healthy volunteers who received health examination at the same time,matching in sex,age were also enrolled as controls.The expression of PD-1 on peripheral blood CD4+T cells and CD8+T cells and PD-L1 on monocytes were detected by flow cytometry.Patients who received chemotherapy alone for 2-4 cycles and received sequential sampling were assessed with Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1).Seven cases of patients with significant response to treatment were selected as partial response (PR) group and ten patients with poor response to treatment were treated as progression disease (PD) group.The differences in the expression of PD-1 on the surface of CD4+T cells,CD8+T cells,and PD-L1 on the surface of monocyte before and after treatment were analyzed.Results Compared with healthy control group,PD-1 expression level on both CD4+ T and CD8+ T cells from peripheral blood in lung cancer group were significantly increased [(25.9±7.4)％ vs (20.6±6.2)％,(19.9±9.8)％ vs (14.0±5.6)％,both P＜0.05].A higher level of PD-L1 expression on monocyte in lung cancer group was also found compared with the control group [(33.1±15.1)％ vs (13.6±5.3)％,P＜0.001].The expression level of PD-1 on CD4+T and CD8+T cells and PD-L1 on monocytes in lung cancer group with good response to treatment was relatively lower than the baseline level of before treatment [(22.8±8.5)％ vs (25.9±7.8)％,(17.1±8.4)％ vs (20.4±8.6)％,(18.1±6.9)％ vs (31.3±13.2)％,all P＜0.05],but in lung cancer group with poor response to treatment,it was higher than the baseline level of before treatment [(33.5±6.5)％ vs (23.9±4.2)％,(25.2±9.1)％ vs (19.1±8.8)％,(43.1±18.3)％ vs (29.7±10.6)％,all P＜0.05].Conclusion Abnormal expression of PD-1 and PD-L1 exists in T cells and monocytes respectively,prompting PD-1/PD-L1 pathway may inhibit T cell proliferation during the interaction of T cell and monocyte,which may lead to non-small cell lung cancer immune escape.%目的 探讨晚期非小细胞肺癌(NSCLC)患者外周血程序性死亡受体1(PD-1)和程序性死亡配体1 (PD-L1)分子的表达及其意义.方法 收集2014年6月至2015年6月苏州大学附属第二医院呼吸科收治的48例晚期NSCLC患者(肺癌组),并选择同期体检中心性别、年龄匹配的36名健康体检者作为对照组.流式细胞学方法检测两组外周血CD4+T细胞、CD8+T细胞表面PD-1的表达百分比和单核细胞表面PD-L1的表达率.将能接受序贯采样的单纯采用化疗治疗2～4周期患者,采用实体瘤疗效评价(RECIST1.1)标准评估病情,筛选疾病部分缓解(PR)者7例为疗效PR组,疾病进展(PD)者10例为疗效PD组,分析两组患者治疗前后CD4+T细胞、CD8+T细胞表面PD-1和单核细胞表面PD-L1的表达差异.结果 肺癌组患者外周血CD4+T和CD8+T细胞表面PD-1表达率均显著高于对照组[(25.9±7.4)％比(20.6±6.2)％,(19.9±9.8)％比(14.0±5.6)％,均P＜0.05];肺癌组外周血单核细胞PD-L1的表达率也显著高于对照组[(33.1±15.1)％比(13.6±5.3)％,P＜0.001].疗效PR组CD4+T、CD8+T细胞表面PD-1和单核细胞表面PD-L1表达率均显著低于治疗前基线水平[(22.8±8.5)％比(25.9±7.8)％、(17.1±8.4)％比(20.4±8.6)％和(18.1±6.9)％比(31.3±13.2)％](均P＜0.05);疗效PD组三者表达率则均显著高于治疗前基线水平[(33.5±6.5)％比(23.9±4.2)％、(25.2±9.1)％比(19.1±8.8)％和(43.1±18.3)％比(29.7±10.6)％](均P＜0.05).结论 NSCLC患者外周血T细胞和单核细胞上存在PD-1和PD-L1的异常表达,提示PD-1/PD-L1信号在T细胞与单核细胞相互作用过程中通过抑制T细胞增殖,参与肺癌细胞免疫逃逸.
